Optimising Breathing Support at Extubation in Very Preterm Infants: A Clinical Study

NCT ID: NCT07251790

Last Updated: 2025-12-26

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 134 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2028-01-31

Brief Summary

Many babies born very preterm (<32 weeks of pregnancy) require support to breathe from a breathing machine (mechanical ventilator) via a breathing tube. Although this keeps babies alive, it can damage their lungs. To reduce this damage, doctors and nurses try to change babies to gentler breathing support that does not require a breathing tube. This is usually done using a method called nasal continuous positive airway pressure (nCPAP) that uses a nosepiece to deliver breaths. This process of removing the breathing tube is called "extubation". Many babies will need the breathing tube put back in after extubation (for various reasons) and this is independently associated with poorer outcomes.

This research study aims to compare two ways of performing extubation - both of which are already used regularly by doctors and nurses. The "standard extubation" approach involves taking a baby's breathing tube out first, then applying the nosepiece and starting nCPAP. The more recent approach, called "prePAP", involves applying the nosepiece and starting nCPAP before taking the breathing tube out. Previous research suggests that a prePAP approach may provide better support for babies during extubation. However, larger studies are required before this approach is more commonly used.

This study is investigating whether extubating the baby with prePAP is better than extubating the baby without prePAP.

The main question it aims to answer is: Does initiating nCPAP before extubation in very preterm babies reduce the fall in their oxygen levels post-extubation?

Detailed Description

The PrePAP trial will investigate if extubation with prePAP (nCPAP commenced prior to extubation) compared to standard extubation practice (nCPAP commenced after extubation) reduces oxygen desaturation in the four hours immediately post-extubation, in very preterm infants being extubated for the first time within the first 30 days of life.

Many infants born very preterm (<32 weeks' gestation) are intubated at birth to receive respiratory support via invasive ventilation. While essential for survival, invasive ventilation can injure their underdeveloped lungs, disrupt lung development and increase the risk of bronchopulmonary dysplasia, a major cause of long-term respiratory morbidity.

Transitioning infants to non-invasive ventilation as soon as feasible is prioritised by clinicians. However, in very preterm infants, almost 40% of extubation attempts fail due to oxygen desaturation or lung collapse. Re-intubation due to extubation failure can induce further airway injury, cardiovascular instability, and oxygen desaturation, resulting in clinical deterioration and prolonged hospitalisation.

PrePAP has been recently suggested as a method of improving respiratory stability during extubation in preterm infants. PrePAP involves commencing nCPAP prior to extubation, with the intent to maintain lung volumes during extubation; preserving oxygenation from pre- to post-extubation. To date, there isn't any clinical evidence explaining the impact to the lungs when both mechanical ventilation and nCPAP are being applied, nor is there evidence that signals a benefit of using prePAP during extubation. Despite this, prePAP is already used in clinical practice and is described in certain neonatal intensive care unit (NICU) extubation guidelines in Australia.

The PrePAP trial is a prospective, multicentre, unblinded, randomised, controlled trial comparing extubation from mechanical ventilation to nCPAP with and without the application of prePAP in very preterm infants born <30 weeks gestational age at first extubation.

Very preterm infants who meet all inclusion (and no exclusion) criteria will be randomised to receive one of two extubation procedures, placing them in either the "Extubation with prePAP" arm or the "Extubation without prePAP" arm:

1. Arm 1: Extubation with prePAP (intervention): nCPAP commenced prior to endotracheal tube removal

2. Arm 2: Extubation without prePAP (control): nCPAP commenced following endotracheal tube removal

For both arms, the intervention period will begin with a 2-to-5-minute pre-extubation period (whilst the infant is still ventilated), followed by a post-extubation period of up to 4 hours, and a follow-up period of up to 7 days (168 hours). The primary outcome (lowest S/F ratio) is assessed only during the (up to) 4-hour post-extubation period.

The results of this trial will determine the appropriate clinical outcomes and end point for a definitive, larger randomised trial to inform clinical practice.

Conditions

Respiratory Distress Syndrome, Newborn; Respiratory Distress Syndrome in Premature Infant

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Extubation with prePAP

nCPAP commenced prior to endotracheal tube removal

Group Type: EXPERIMENTAL

Pre-extubation continuous positive airway pressure

Intervention Type: PROCEDURE

Prior to extubation (2-to-5 minutes) a CPAP hat will be placed on the infant and the circuit set up. A nasal mask will be applied and nCPAP pressure will be commenced at 10 centimetres of water. Only after nCPAP has been in situ for 2 minutes (maximum 5 minutes) will the endotracheal tube be removed.

Extubation without prePAP

nCPAP commenced following endotracheal tube removal

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Pre-extubation continuous positive airway pressure

Prior to extubation (2-to-5 minutes) a CPAP hat will be placed on the infant and the circuit set up. A nasal mask will be applied and nCPAP pressure will be commenced at 10 centimetres of water. Only after nCPAP has been in situ for 2 minutes (maximum 5 minutes) will the endotracheal tube be removed.

Intervention Type: PROCEDURE

Other Intervention Names

PrePAP

Eligibility Criteria

Inclusion Criteria

• The infant is admitted to participating NICU
• The infant is born between 22+0 to 29+6 weeks gestational age
• The infant has been on a form of invasive mechanical ventilation for at least 4 hours
• The infant is being electively extubated for the first time from invasive mechanical ventilation to nCPAP
• The infant is being electively extubated for the first time within 30 days from birth
• The infant is clinically stable (as per clinical and research team consensus)
• The parent(s) or legal guardian(s) provides prospective informed consent.

Exclusion Criteria

• The infant is born <22 weeks or >30 weeks gestational age
• The infant has a major congenital anomaly involving the cardiac, respiratory or gastrointestinal systems, or a known genetic syndrome or diagnosis that might affect respiratory course and outcomes
• The infant has severe pulmonary hypoplasia due to anhydramnios or oligohydramnios before 22 weeks in which the neonatal clinician anticipates that pulmonary hypoplasia related respiratory failure will be the major respiratory problem in early postnatal life
• The infant is receiving invasive mechanical ventilation via nasotracheal intubation
• The infant is planned for extubation to any other mode of non-invasive respiratory support than nCPAP, or no respiratory support
• Refusal of informed consent from the parent(s), or the infant does not have a guardian who can provide informed consent.

• Minimum Eligible Age: 0 Hours
• Maximum Eligible Age: 30 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Western Health, Australia

OTHER_GOV

Sponsor Role: collaborator

Royal Women's Hospital, Melbourne, Australia

UNKNOWN

Sponsor Role: collaborator

Murdoch Childrens Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Georgia S Stephen, BBmedSc BBiomedSc(Hons)

Role: PRINCIPAL_INVESTIGATOR

Murdoch Childrens Research Institute

Locations

The Royal Women's Hospital

Melbourne, Victoria, Australia

Joan Kirner Women's and Children's Hospital

Saint Albans, Victoria, Australia

Countries

Australia

Central Contacts

Georgia S Stephen, BBmedSc BBiomedSc(Hons)

Role: CONTACT

Phone: 424701924

Email: georgia.stephen@mcri.edu.au

Facility Contacts

Risha Bhatia, MBBCh MA FRACP PhD

Role: primary

Georgia S Stephen, BBmedSc BBiomedSc(Hons)

Role: backup

Arun Sett, MBBS(Hons) FRACP PhD

Role: primary

Georgia S Stephen, BBmedSc BBiomedSc(Hons)

Role: backup

References

Gaertner VD, Ruegger CM. Optimising success of neonatal extubation: Respiratory support. Semin Fetal Neonatal Med. 2023 Oct;28(5):101491. doi: 10.1016/j.siny.2023.101491. Epub 2023 Nov 18.

Reference Type: BACKGROUND

PMID: 37993322 (View on PubMed)

Bhatia R, Carlisle HR, Armstrong RK, Kamlin COF, Davis PG, Tingay DG. Extubation generates lung volume inhomogeneity in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2022 Jan;107(1):82-86. doi: 10.1136/archdischild-2021-321788. Epub 2021 Jun 23.

Reference Type: BACKGROUND

PMID: 34162692 (View on PubMed)

Plastina L, Gaertner VD, Waldmann AD, Thomann J, Bassler D, Ruegger CM. The DELUX study: development of lung volumes during extubation of preterm infants. Pediatr Res. 2022 Jul;92(1):242-248. doi: 10.1038/s41390-021-01699-w. Epub 2021 Aug 31.

Reference Type: BACKGROUND

PMID: 34465873 (View on PubMed)

Other Identifiers

120475

Identifier Type: -

Identifier Source: org_study_id